PUBLICATION

Tuba1a gene expression is regulated by KLF6/7 and is necessary for CNS development and regeneration in zebrafish

Authors

Veldman, M.B., Bemben, M.A., and Goldman, D.

ID

ZDB-PUB-100211-4

Date

2010

Source

Molecular and cellular neurosciences 43(4): 370-383 (Journal)

Registered Authors

Goldman, Dan, Veldman, Matt

Keywords

Retina, Retinal ganglion cell, Tubulin, KLF, Optic nerve, p27, Promoter

MeSH Terms

Animals
Nerve Tissue Proteins/genetics
Nerve Tissue Proteins/metabolism*
Promoter Regions, Genetic/genetics
Nerve Regeneration/physiology*
Reverse Transcriptase Polymerase Chain Reaction
In Situ Hybridization
Optic Nerve Injuries/metabolism*
Tubulin/genetics*
Tubulin/metabolism
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Gene Expression Regulation
Electrophoretic Mobility Shift Assay
Animals, Genetically Modified
Immunohistochemistry
Zebrafish
RNA, Messenger/genetics
RNA, Messenger/metabolism
Retina/metabolism*

(all 20)

PubMed

20123021 Full text @ Mol. Cell Neurosci.

Abstract

We report that knockdown of the alpha1 tubulin isoform Tuba1a, but not the highly related Tuba1b, dramatically impedes nervous system formation during development and RGC axon regeneration following optic nerve injury in adults. Within the tuba1a promoter, a G/C-rich element was identified that is necessary for tuba1a induction during RGC differentiation and optic axon regeneration. KLF6a and 7a, which we previously reported are essential for optic axon regeneration (Veldman et al., 2007), bind this G/C-rich element and transactivate the tuba1a promoter. In vivo knockdown of KLF6a and 7a attenuate regeneration-dependent activation of the endogenous tuba1a and p27 genes. These results suggest tuba1a expression is necessary for CNS development and regeneration and that KLF6a and 7a mediate their effects, at least in part, via transcriptional control of tuba1a promoter activity.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
cdkn1bb	mi2Tg	standard conditions	Adult		retina	RTPCR	Fig. 10
cdkn1bb	mi2Tg	surgical manipulation: cranial nerve II	Adult		retina	RTPCR	Fig. 10
cdkn1bb	mi2Tg + MO1-klf6a + MO1-klf7b + MO2-klf6a + MO2-klf7b	surgical manipulation: cranial nerve II	Adult		retina	RTPCR	Fig. 10
EGFP	mi22Tg	standard conditions	Prim-25		central nervous system	IFL	Fig. 7
EGFP	mi22Tg	standard conditions	Long-pec	Not Detected	retina	IFL	Fig. 7
EGFP	mi22Tg	standard conditions	Adult	Not Detected	retinal ganglion cell layer	IFL	Fig. 7
EGFP	mi22Tg	surgical manipulation: cranial nerve II	Adult	Not Detected	retinal ganglion cell layer	IFL	Fig. 7
EGFP	mi23Tg	standard conditions	Prim-25		central nervous system	IFL	Fig. 7
EGFP	mi23Tg	standard conditions	Long-pec		retina	IFL	Fig. 7
EGFP	mi23Tg	standard conditions	Adult	Not Detected	retinal ganglion cell layer	IFL	Fig. 7

1 - 10 of 48

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-tuba1a	standard conditions	Prim-15	apoptotic process increased occurrence, abnormal	Fig. 3
WT + MO1-tuba1a	standard conditions	Prim-15	brain development disrupted, abnormal	Fig. 3
WT + MO1-tuba1a	standard conditions	Prim-15	brain morphology, abnormal	Fig. 3
WT + MO1-tuba1a	standard conditions	Prim-15	embryo development process quality, abnormal	Fig. 3
WT + MO1-tuba1a	standard conditions	Prim-15	retina development in camera-type eye disrupted, abnormal	Fig. 3
WT + MO1-tuba1a	standard conditions	Prim-15	retina morphology, abnormal	Fig. 3
WT + MO1-tuba1a	standard conditions	Prim-25	whole organism dead, abnormal	Fig. 3
WT + MO1-tuba1a	standard conditions	Prim-25	whole organism viability, abnormal	Fig. 3
WT + MO1-tuba1b	standard conditions	Prim-15	whole organism morphology, normal	Fig. 3
WT + MO2-tuba1a	standard conditions	Prim-15	apoptotic process increased occurrence, abnormal	Fig. 3

1 - 10 of 18

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Mutations / Transgenics

Allele	Construct	Type
mi2Tg	Tg(-1.7Cau.Tuba1:GFP)	Transgenic Insertion
mi22Tg	Tg3(-1.7Cau.Tuba1:EGFP)	Transgenic Insertion
mi23Tg	Tg4(-1.7Cau.Tuba1:EGFP)	Transgenic Insertion
mi24Tg	Tg5(-1.7Cau.Tuba1:EGFP)	Transgenic Insertion
mi29Tg	Tg6(-1.7Cau.Tuba1:EGFP)	Transgenic Insertion

1 - 5 of 5

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
klf6a	MO1-klf6a	MRPHLNO
klf6a	MO2-klf6a	MRPHLNO
klf7b	MO1-klf7b	MRPHLNO
klf7b	MO2-klf7b	MRPHLNO
tuba1a	MO1-tuba1a	MRPHLNO
tuba1a	MO2-tuba1a	MRPHLNO
tuba1b	MO1-tuba1b	MRPHLNO
tuba1b	MO2-tuba1b	MRPHLNO

1 - 8 of 8

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Fish

Fish
mi2Tg
mi2Tg + MO1-klf6a + MO1-klf7b + MO2-klf6a + MO2-klf7b
mi22Tg
mi23Tg
mi24Tg
mi29Tg
WT
WT + MO1-tuba1a
WT + MO1-tuba1b
WT + MO2-tuba1a

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GFP	EFG	GFP

Mapping

Veldman et al., 2010 ZDB-PUB-100211-4 PMID:20123021

Tuba1a gene expression is regulated by KLF6/7 and is necessary for CNS development and regeneration in zebrafish

Veldman et al., 2010

ZDB-PUB-100211-4
PMID:20123021